1. Field of the Invention
The present invention relates to a novel process for the synthesis of 2,3-dimethoxy-5-methyl-6-substituted-1,4-benzoquinones having the formula (I): ##STR5## wherein R is ##STR6## in which n is an integer of 0 to 9, and A and B are hydrogens or A-B together form a direct valence bond between the two carbon atoms to which they are attached.
Compounds of formula (I) are known as coenzymes Q, and especially, 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone [2,3-dimethoxy-5-methyl-6-(3,7,11,15,19,23,27 31,34,39-decamethyltetracontadecaen-2,6,10,14,18,22,26,30, 34,38-yl)-1,4-benzoquinone ] in which A-B is a direct valence bond and n is 9, which is called "coenzyme Q.sub.10 ", participates in the electron transport system in living bodies and plays an important role for producing energy. This compound has activities of improving the state of the myocardium in patients suffering from ischemia, increasing the reduced heart beat number and competing with the Na-storage action of aldosterone, and is effective for treating and preventing congestive heart failure, lung congestion, swelling of the liver and angina pectoris.
2. Description of the Prior Art
As known processes for the synthesis of compounds of formula (I), there can be mentioned a method comprising reacting 2,3-dimethoxy-6-methyl-1,4-benzohydroquinone or a 1-monoacyl derivative thereof with an n- or iso-prenol or a reactive derivative thereof, in the presence of an acid catalyst such as a protonic acid, e.g., formic acid, sulfuric acid, hydrochloric acid, phosphoric acid, p-toluene-sulfonic acid or the like, a Lewis acid, e.g., zinc chloride, a boron trifluoride-ether complex or the like, or a mixture of these protonic or Lewis acids, to obtain a corresponding hydroquinone (see Japanese Patent Publications No. 17513/64 and No. 3967/71), and reacting the hydroquinone with an oxidizing agent to convert it to a corresponding benzoquinone (see Japanese Patent Publication No. 17514/64). In such known method, however, because the yield in the condensation step is low, the yield of the intended quinone compound is very low and even the yield of the crude product is about 30% at the highest. Further, each of the acid catalysts that are used in the condensation step is highly corrosive and has a bad effect on the equipment, and metal dissolved out from the acid catalyst contaminates the product. Accordingly, industrial working of this known method involves various disadvantages.
Further, since an acid catalyst such as mentioned above is employed, neutralization, extraction and other post treatments must be conducted for separating the desired product from the reaction mixture, and since the amount of the catalyst used for the reaction is relatively large and the catalyst used must often be discarded after completion of the reaction, the manufacturing cost is increased and environmental pollution is readily caused. Thus, this known method involves various industrial difficulties.